The applicant proposes a comprehensive program for development as a clinical investigator, reflecting his interest and expertise in pediatric infectious diseases and pediatric hematology. Under the mentorship of Dr Jim Eckman, a senior Nationally recognized investigator in the area of Sickle Cell Disease, and co- mentorship of two investigator in pediatric infectious disease at Emory University, the applicant will pursue a focused clinical research project and will receive formal and practical instruction in all aspects of clinical investigation. The rich academic environment, including the Emory University School of Medicine and School of Public Health (SPH), the Centers for Disease Control and Prevention (CDC), one of the country's largest comprehensive pediatric SCD clinics and the Emory Vaccine Center, is a remarkable resource for the applicant's optimal development as a pediatric clinical investigator. The applicant is interested in developing more effective prevention strategies of Streptococcus pneumoniae infections in children with sickle cell disease (SCD), inasmuch as these infections remain a major cause of morbidity and mortality in these children. In a recent prospective multicenter survey, the applicant has shown that over 40 percent of S. pneumoniae isolates in children with SCD are now no longer susceptible to penicillin. This rapid increase in penicillin resistance warrants evaluation of more effective prophylaxis of S. pneumoniae infections, to be used in addition to or possibly instead of penicillin prophylaxis. The hypothesis of the applicant project is that protein conjugated vaccines will offer effective protective immunity to children with SCD against S. pneumoniae infections. To test this hypothesis the applicant will conduct a prospective study of the efficacy of this protein conjugate vaccine in pediatric SCD patients. To facilitate this project, the applicant has organized a collaborative network of several major pediatric SCD centers and enlisted the collaboration of senior pediatric clinical investigators who direct those centers. The specific aims of this project are to estimate the conjugate vaccine efficacy in children with SCD by comparing rates of S. pneumoniae infections occurring before and after vaccine introduction in the general population (expected licensure in 2000). In this once in a life time "natural" experiment, the applicant will characterize the specific S. pneumoniae isolates, including serotype distribution and antibiograms. The applicant will also evaluate immunity by laboratory assays (ELISA, functional, and T and B cell memory) following vaccination in children with SCD. This project will be conducted within the framework of a recently formed and CDC funded Emory Consortium (PI: Dr Harry Keyserling). Results from these studies will provide the foundation for future clinical care recommendations to prevent this most lethal complication of childhood SCD. Through the course of this trial, the applicant will enhance and develop clinical research expertise by interactions with colleagues at the CDC and the National Institutes of Health, and with vaccine trial researchers and members of the pharmaceutical industry. To complement his stewardship of a focused clinical research project, he will participate in didactic coursework offered by the Emory University SPH, including biostatistics, epidemiology, clinical trial design, and information systems/database management. Practical instruction in the ethics of informed consent and evaluation of clinical trial design and methods will be obtained through an internship at the Human Investigations Committee of Emory University. A motivated and creative applicant, dedicated mentorship, formal educational opportunities, and an innovative clinical study are factors that indicate the tremendous potential for the applicant's successful career development as a thoughtful, well-trained pediatric clinical investigator.